Publications by authors named "Cesar Koppe Grisolia"

55 Publications

Andiroba oil and nanoemulsion (Carapa guianensis Aublet) reduce lesion severity caused by the antineoplastic agent doxorubicin in mice.

Biomed Pharmacother 2021 Jun 24;138:111505. Epub 2021 Mar 24.

Laboratório de Citogenética, Centro de Estudos Avançados da Biodiversidade, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. Electronic address:

Doxorubicin (DOX) is an anthracycline antibiotic used in the fight against many types of cancer. Although it is quite effective for this purpose, its clinical use is limited by its severe side effects, highlighting the relevance of efforts to identify substances that act to minimize these effects. In this work, we sought to verify the ability of andiroba oil (AO) and a nanoemulsion of andiroba oil (AN) to lessen the side effects of DOX. The animals were separated into 7 groups with 6 animals each: mice treated with AO (2000 mg/kg), AN (2000 mg/kg), the antineoplastic agent DOX (40 mg/kg), AO+DOX, AN+DOX and solvent controls was used of negative control (corn oil and nanoemulsion surfactant). AO and AN were administered for 14 consecutive days orally by gavage and on the 13th day, applied DOX by intraperitoneal route (i.p.), in order to evaluate the protective potential of andiroba. The animals were euthanized on the 15th day. Hematological, biochemical, histological, and immunohistochemical parameters were analyzed. Andiroba reduced several aspects of the severity of lesions caused by DOX, decreasing hematotoxicity and the severity of histological changes in the liver and kidneys, and reducing the frequency of apoptotic cell death. In many cases, AN showed greater efficacy than AO alone, reflecting the feasibility of using this nanotechnology to improve the pharmacokinetics of lipid compounds in the body. The study sheds new light on the therapeutic benefits of andiroba and suggests new ways for investigating how the quantity and quality of lipid compounds affect exposed organisms.
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http://dx.doi.org/10.1016/j.biopha.2021.111505DOI Listing
June 2021

Degradation evaluation and toxicity profile of bilobol, a promising eco-friendly larvicide.

Chemosphere 2021 Jan 16;263:128323. Epub 2020 Sep 16.

Universidade de Brasília, Laboratório de Farmacognosia, Campus Universitário Darcy Ribeiro, 70910-900, Brasília, DF, Brazil. Electronic address:

Aedes aegypti is the main arbovirus vector transmitting chikungunya, Zika and dengue. The current vector control strategies are limited due to multiple insecticide resistance, deleterious impacts on the environment, and toxicity to non-target organisms. Bilobol, an alkylresorcinol isolated from the plant species Schinus terebinthifolia, demonstrated larvicidal activity against Aedes aegypti (LC 7.67 mg/L in less than 24 h). To ensure that bilobol presents a viable alternative as an eco-friendly larvicide, this study aimed to explore the degradation process and acute toxicity of this alkylresorcinol in zebrafish, a non-target organism. A quantification method with validated parameters was developed and used to evaluate bilobol degradation in water over time. The Fish Embryo Toxicity (FET) test was applied to evaluate the acute toxicity of bilobol together with its degradation derivates. Results demonstrated that bilobol gradually degrades over time and almost completely disappears after 96 h, turning into small aliphatic chains which are less toxic than bilobol in its fundamental form. Therefore, it was possible to conclude that bilobol does not present significant toxicity to zebrafish embryos nor does it show signs of persistence in the environment. Additionally, bilobol can be found in high quantities not only in S. terebinthifolia, but also in cashew nut industry waste. Thus, bilobol constitutes an alternative environmentally friendly insecticide because it is not persistent, has indications of low toxicity to non-target organisms and presents a way to exploit massive quantities of material discarded by the food industry.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128323DOI Listing
January 2021

Auramine dyes induce toxic effects to aquatic organisms from different trophic levels: an application of predicted non-effect concentration (PNEC).

Environ Sci Pollut Res Int 2021 Jan 28;28(2):1866-1877. Epub 2020 Aug 28.

Faculdade de Tecnologia, Universidade Estadual de Campinas, UNICAMP, Limeira, SP, Brazil.

The dyes Auramine and Auramine O are used in several industrial products, despite the scarce information regarding their ecotoxicity. The aim of the present study was to assess the acute and chronic toxicity of both dyes to aquatic organisms from different trophic levels (Raphidocelis subcapitata, Daphnia similis, Hydra attenuata, and Danio rerio) and calculate their predicted non-effect concentrations (PNEC). Auramine and Auramine O induced toxicity to all selected test organisms with L(E)C50 values ranging from 300 to 4800 ug/L. Both dyes induced inhibition in the growth rate of exposed algae, negatively affecting the reproduction of D. similis and induced deformities in H. attenuata (clubbed tentacles and shortened tentacles) and D. rerio (edemas, tail malformation and delay in yolk sac absorption). PNEC values of 0.92 μg/L and 4.0 μg/L were obtained for Auramine and Auramine O, respectively, based on results of the most sensitive test system (algae). Test results were analyzed using the Criteria of Reporting and Evaluating Ecotoxicity Data (CRED), confirming their reliability and relevance. Thus, PNEC values can be used in future risk assessments of those substances in freshwater systems.
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http://dx.doi.org/10.1007/s11356-020-10462-3DOI Listing
January 2021

Steroid androgen 17 alpha methyltestosterone used in fish farming induces biochemical alterations in zebrafish adults.

J Environ Sci Health A Tox Hazard Subst Environ Eng 2020 11;55(11):1321-1332. Epub 2020 Jul 11.

Department of Genetics and Morphology, Institute of Biological Sciences, Universidade de Brasília, Brasília, DF, Brazil.

The 17 alpha methyltestosterone (MT) hormone is fed to larvae in fish farms with the purpose of inducing sex reversal. The aim of this study was to evaluate the toxicity and sub-lethality of MT (99.9% purity) and cMT (a commercial MT with 90% purity) in zebrafish () adults, where the animals were exposed to concentrations of 0, 4, 23, 139, 833 and 5000 µg/L for 96 hours. Genotoxicity was evaluated by micronucleus test (MN), nuclear abnormalities (NA) and comet assay. A low genotoxic potential of MT was showed, inducing micronucleus, nuclear abnormalities and DNA damage in , depending on the use of MT or cMT, gender and tested concentrations. In the sub-lethality trials, there was a basal difference in the activity of the enzymatic biochemical markers for males and females, while the Glutatione S transferase (GST) activity decreased in all analyzed tissues, and for males the enzymatic activity decreased only in the intestine. Results suggest that MT has a toxic potential to fish because it alters enzymatic metabolic pathways and may pose a risk to the ecosystems.
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http://dx.doi.org/10.1080/10934529.2020.1790954DOI Listing
October 2020

Fluoxetine chronic exposure affects growth, behavior and tissue structure of zebrafish.

Comp Biochem Physiol C Toxicol Pharmacol 2020 Nov 22;237:108836. Epub 2020 Jun 22.

Laboratório de Genética Toxicológica, Departamento de Genética e Morfologia, Instituto de Biologia, Universidade de Brasília, Asa Norte, 70910-900 Brasília, Distrito Federal, Brazil. Electronic address:

Fluoxetine (FLX) is among the top 100 pharmaceutical prescribed annually worldwide and consequently is often detected in wastewater treatment plant effluent and surface waters, in concentrations up to 2.7 and 0.33 μg/L, respectively. Despite the presence of FLX in surface waters, little is known about its chronic effects in fish. Thus, this study aimed at investigating the chronic toxicity of FLX to Danio rerio adults. Rate of weight gain, behavior (feeding and swimming activity) and tissue organization (liver and intestine) were evaluated, after 30 days exposure. A lower rate of weight gain was observed at 100 μg/L FLX. The food intake time decreased, showing a decrease in fish appetite. The preference for the upper aquarium layer was observed at 10 and 100 μg/L of FLX, indicating an inhibition of the stress level (anxiolytic effect). Mild to moderate damage of hepatic tissue and a decrease epithelium height and increase in villus height of intestine were observed in fish exposed to concentrations as low as 0.01 μg/L. Based on obtained results, chronic exposure of fish to FLX could affect swimming and feeding behavior and alter morphological structure of liver and intestine tissues at environmental levels.
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http://dx.doi.org/10.1016/j.cbpc.2020.108836DOI Listing
November 2020

Impact of the glyphosate-based commercial herbicide, its components and its metabolite AMPA on non-target aquatic organisms.

Mutat Res 2019 06 4;842:94-101. Epub 2019 May 4.

Faculty of Pharmacy, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil; National Institute for Alternative Technologies of Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactives (INCT-DATREM), UNESP, Institute of Chemistry, P.O. Box 355, 14800-900 Araraquara, SP, Brazil. Electronic address:

Glyphosate (GLY) is the active ingredient of several herbicide formulations widely used to control weeds in agricultural and non-agricultural areas. Due to the intensive use of GLY-based herbicides and their direct application on soils, some of their components, including the active ingredient, may reach the aquatic environment through direct run-off and leaching. The present study assessed the acute toxicity and genotoxicity of the GLY-based formulation Atanor 48 (ATN) and its major constituents GLY, surfactant polyethoxylated tallow amine (POEA), as well as the main metabolite of GLY aminomethylphosphonic acid (AMPA) on non-target aquatic organisms. The toxic effects of these chemicals were evaluated in the fish embryo acute toxicity test with zebrafish (Danio rerio), while genotoxic effects were investigated in the comet assays with cells from zebrafish larvae and rainbow trout gonad-2 (RTG-2). GLY and AMPA caused no acute toxic effect, while ATN and POEA induced significant lethal effects in zebrafish (LC-96 h 76.50 mg/L and 5.49 mg/L, respectively). All compounds were genotoxic in comet experiments with zebrafish larvae (LOEC 1.7 mg/L for GLY, ATN, AMPA and 0.4 mg/L for POEA). Unlike in vivo, only POEA induced DNA damage in RTG-2 cells (LOEC 1.6 mg/L), suggesting that it is a direct acting genotoxic agent. In summary, these data indicate that the lethal effects on zebrafish early-life stages can be ranked in the following order from most to least toxic: surfactant POEA > formulation ATN > active ingredient GLY ≈ metabolite AMPA. Genotoxic effects were observed in both RTG-2 cells (only POEA) and zebrafish (all test compounds) with the lowest tested concentrations. Therefore, it is important to evaluate different toxicological endpoints as well as use different non-target organisms to predict the hazards of GLY-based formulations and their components and breakdown product to aquatic biota.
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http://dx.doi.org/10.1016/j.mrgentox.2019.05.002DOI Listing
June 2019

Toxicological findings about an anticancer fraction with casearins described by traditional and alternative techniques as support to the Brazilian Unified Health System (SUS).

J Ethnopharmacol 2019 Sep 29;241:112004. Epub 2019 May 29.

Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.

Ethnopharmacological Relevance: Extracts, essential oils and molecules from Casearia sylvestris have popularly shown pharmacological actions against chronic diseases, as anxiety, inflammation, cancer and dyslipidemia. In the context of antitumoral therapy, we investigated in vitro, ex vivo and in vivo toxicological changes induced by a Fraction with Casearins (FC) and its component Casearin X isolated from C. sylvestris on animal and vegetal cells, and upon invertebrates and mammals.

Material And Methods: Cytotoxicity was carried out using normal lines and absorbance and flow cytometry techniques, Artemia salina nauplii, Danio rerio embryos and meristematic cells from Allium cepa roots. Acute and 30 days-mice analysis were done by behavioral, hematological and histological investigations and DNA/chromosomal damages detected by alkaline Cometa and micronucleus assays.

Results: FC was cytotoxic against lung and fibroblasts cells and caused DNA breaks, loss of integrity and mitochondrial depolarization on ex vivo human leukocytes. It revealed 24 h-LC values of 48.8 and 36.7 μg/mL on A. salina nauplii and D. rerio embryos, reduced mitotic index of A. cepa roots, leading to cell cycle arrest at metaphase and anaphase and micronuclei. FC showed i.p. and oral LD values of 80.9 and 267.1 mg/kg body weight. Subacute i.p. injections induced loss of weight, swelling of hepatocytes and tubules, tubular and glomerular hemorrhage, microvesicular steatosis, lung inflammatory infiltration, augment of GPT, decrease of albumin, alkaline phosphatase, glucose, erythrocytes, and lymphocytes, and neutrophilia (p > 0.05). FC-treated animals at 10 mg/kg/day i.p. caused micronuclei in bone marrow and DNA strand breaks in peripheral leukocytes.

Conclusions: This research postulated suggestive side effects after use of FC-related drugs, demonstrating FC as antiproliferative and genotoxic on mammal and meristematic cells, including human leukocytes, teratogenicity upon zebrafish embryos, myelosuppression, clastogenicity, and morphological and biochemical markers indicating liver as main target for FC-induced systemic toxicity.
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http://dx.doi.org/10.1016/j.jep.2019.112004DOI Listing
September 2019

CNTs coated charcoal as a hybrid composite material: Adsorption of fluoxetine probed by zebrafish embryos and its potential for environmental remediation.

Chemosphere 2019 Sep 10;230:369-376. Epub 2019 May 10.

Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Genética & Morfologia, Brasília, DF, Brazil.

Although traditional water treatment systems can remove various substances from wastewater, these conventional systems fail to remove many chemical molecules that pose potential ecological and health risks. Carbon nanotubes (CNTs) appear attractive to adsorption of many substances, but CNTs adsorbed with toxic substances becomes a nanocomposite still more toxic. Here, we employ zebrafish embryos as biosensor to examine how a hybrid micro/nanostructured carbonaceous material (HMNC) derived from a combination of activated carbon (AC) with hydrophilic carbon nanotubes (CNTs) can remediate wastewater contaminated with the pharmaceutical fluoxetine hydrochloride (FLX). AC and HMNC are practically non-toxic to zebrafish embryos (LC > 1000 mg.L). HMNC addition to culture medium containing FLX significantly reduces sublethal effects and lethality. Interaction between FLX and HMNC involves chemical adsorption such that embryo co-exposure to HMNC adsorbed with FLX in the range of concentrations evaluated herein does not elicit any behavioral changes in zebrafish.
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http://dx.doi.org/10.1016/j.chemosphere.2019.05.019DOI Listing
September 2019

Effects of AgNPs on the Snail : Survival, Reproduction and Silver Accumulation.

Toxics 2019 Mar 1;7(1). Epub 2019 Mar 1.

Instituto de Ciências Biológicas, Departamento de Genética e Morfologia, Universidade de Brasília (UnB), Brasília, DF 70910-900, Brazil.

Silver nanoparticles (AgNPs) are used intensively in medical and industrial applications. Environmental concerns have arisen from the potential release of this material into aquatic ecosystems. The aims of this research were to evaluate the potential accumulation of silver in the whole body of organisms and analyze the effects of AgNPs on the survival and reproduction of the snail . Results show slow acute toxicity with a 10-day LC of 18.57 mg/L and an effective decrease in the eggs and egg clutches per organism exposed to tested concentrations. Based on these data, the No Observed Effect Concentration (NOEC) observed was <1 mg/L for snail reproduction. For silver accumulation, we observed that uptake was faster than elimination, which was very slow and still incomplete 35 days after the end of the experiment. However, the observed accumulation was not connected with a concentration/response relationship, since the amount of silver was not equivalent to a higher reproductive effect. The data observed show that AgNPs are toxic to , and suggest that the snail has internal mechanisms to combat the presence of Ag in its body, ensuring survival and reduced reproduction and showing that the species seems to be a potential indicator for Ag presence in contaminated aquatic ecosystems.
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http://dx.doi.org/10.3390/toxics7010012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468862PMC
March 2019

In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes.

Dalton Trans 2019 May;48(18):6026-6039

Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goias-UFG, CEP 74690-900 Goiania, Goias, Brazil.

In this paper, four new ruthenium complexes, [Ru(N-S)(dppm)2]PF6 (1), [Ru(N-S)(dppe)2]PF6 (2), [Ru(N-S)2(dppp)] (3) and [Ru(N-S)2(PPh3)2] (4) [dppm = 1,1-bis(diphenylphosphino)methane, dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, PPh3 = triphenylphosphine and N-S = 2-mercaptopyrimidine anion] were synthesized and characterized using spectroscopy techniques, molar conductance, elemental analysis, electrochemical techniques and X-ray diffraction. The DNA binding studies were investigated using voltammetry and spectroscopy techniques. The results show that all complexes exhibit a weak interaction with DNA. HSA interaction with the complexes was studied using fluorescence emission spectroscopy, where the results indicate a spontaneous interaction between the species by a static quenching mechanism. The cytotoxicity of the complexes was evaluated against A549, MDA-MB-231 and HaCat cells by MTT assay. Complexes (1) and (2), which are very active against triple negative MDA-MB-231, were subjected to further biological tests with this cell line. The cytotoxic activity triggered by the complexes was confirmed by clonogenic assay. Cell cycle analyses demonstrated marked anti-proliferative effects, especially at the G0/G1 and S phases. The morphological detection of apoptosis and necrosis - HO/PI and Annexin V-FITC/PI assay, elucidated that the type of cell death triggered by these complexes was probably by apoptosis. The in vivo toxicological assessment performed on zebrafish embryos revealed that complexes (1) and (2) did not present embryotoxic or toxic effects during embryonic and larval development showing that they are promising new prototypes of safer and more effective drugs for triple negative breast cancer treatment.
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http://dx.doi.org/10.1039/c8dt03738hDOI Listing
May 2019

Exposure to dilute concentrations of bupropion affects zebrafish early life stages.

Chemosphere 2019 May 25;222:175-183. Epub 2019 Jan 25.

Laboratório de Genética Toxicológica, Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, UnB, 70910-900, Brasília, Distrito Federal, Brazil. Electronic address:

Psychiatric pharmaceuticals are one of the most prescribed active substances globally. Bupropion (BPP) is an antidepressant that acts via inhibition of norepinephrine and dopamine reuptake. It has been found in various water matrices, and thus its effects on aquatic organisms must be studied. The present study aimed to evaluate the acute toxic effects of BPP on zebrafish (Danio rerio) early life stages. For developmental analysis, organisms were exposed for 168 h to concentrations ranging from 0 to 82000 μg/L. Two other experiments were performed by exposing embryos to a wide range of concentrations (from 0 to 50000 μg/L) in order to evaluate BPP effects on embryonic behavior, using the Zebrabox and testing at the biochemical level (acetylcholinesterase, glutathione-S-transferase, lactate dehydrogenase and catalase). Developmental analysis indicated that BPP had low acute toxicity with a calculated 168 h-LC50 of 50346 μg/L. Concentrations equal to or above 44800 μg/L elicited several effects such as hatching delay, edemas and tail deformities. However, concentrations from 7300 μg/L upwards elicited equilibrium alteration. Behavioral analysis showed that BPP affected zebrafish locomotor behavior by decreasing activity at 0.6 μg/L, increasing activity at 8.8 and 158 μg/L, and decreasing activity at 50000 μg/L. Biochemical analysis showed an increase of AChE activity at 158 and 2812 μg/L, an increase in GST at the highest concentrations, CAT alteration and increase of LDH at 0.6, 2812 and 50000 μg/L. We can conclude that BPP affects zebrafish early life stages at environmental concentrations.
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http://dx.doi.org/10.1016/j.chemosphere.2019.01.141DOI Listing
May 2019

Why pesticides with mutagenic, carcinogenic and reproductive risks are registered in Brazil.

Dev World Bioeth 2019 09 6;19(3):148-154. Epub 2018 Dec 6.

Brazil is the biggest market for pesticides in the world. In the registration process, a pesticide must be authorized by the Institute of the Environment, Health Surveillance Agency and Ministry of Agriculture. Evaluations follow a package of toxicological studies submitted by the companies and also based on the Brazilian law regarding pesticides. We confronted data produced by private laboratories, submitted to the Institute of the Environment for registration, with data obtained from scientific databases, corresponding to mutagenicity, carcinogenicity and teratogenicity of pesticides. All studies submitted by the companies were carried out by private laboratories. From 247 pesticide formulations analyzed, none showed positive results for mutagenicity, carcinogenicity or teratogenicity. From 574 articles in the scientific literature, 84% published by public laboratories showed positive results, while 79% of those showing negative results came from private laboratories. There is an ethical concern about a conflict of interest between public/independent laboratories and private laboratories that produce data for registering pesticides. We demonstrated that there is a clear contradiction between public and private laboratories. Brazilian regulatory authorities have approved the registration of pesticides based almost exclusively on the monographs provided by the pesticide industry, because the use of scientific articles or information from the independent literature is strongly belittled by the industry. Pesticide companies argue that scientific articles cannot be trusted. Also, according to the industry, pesticide registration cannot be refused based on results from scientific articles. Thus, the registration of pesticides with mutagenic, carcinogenic and teratogenic risks has been approved in Brazil.
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http://dx.doi.org/10.1111/dewb.12211DOI Listing
September 2019

The pequi pulp oil (Caryocar brasiliense Camb.) provides protection against aging-related anemia, inflammation and oxidative stress in Swiss mice, especially in females.

Genet Mol Biol 2018 Oct-Dec;41(4):858-869. Epub 2018 Nov 29.

Departmento de Genética e Morfologia, Instituto de Ciências Biologicas, Universidade de Brasília, Brasilia, DF, Brazil.

Continued exposure to reactive oxygen species and inflammation are the rationale behind aging theories and associated diseases. Scientific evidence corroborates the ethnomedicinal use of the oil of pequi (Caryocar brasiliense Camb.), a typical Brazilian Cerrado fruit, against oxidative damage to biomolecules and inflammation. We aimed to investigate in vivo the antioxidant and anti-inflammatory effects of pequi oil on hemogram and DNA damage in healthy young adult and older middle-aged Swiss mice of both genders. Animals, aged 6-7 and 11-12 months, were orally treated for 15 days with pequi oil at 30 mg/day. Blood samples were used for hemogram and comet assay, and bone marrow for micronucleus test. Female controls of 11-12 months had significantly lower haemoglobin and hematocrit than those of 6-7 months. Treatment with pequi oil improved this state, removing the differences. Pequi oil had no genotoxic or clastogenic effects and significantly increased lymphocytes and decreased neutrophils+monocytes in females of 11-12 months, removing the significant differences observed between controls of 6-7 and 11-12 months. The results suggest that dietary supplementation with pequi oil could protect against anemia, inflammation and oxidative stress related to aging, helping to prevent aging-related chronic degenerative diseases, mainly for females.
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http://dx.doi.org/10.1590/1678-4685-GMB-2017-0218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415600PMC
November 2018

Acute toxic effects of ruthenium (II)/amino acid/diphosphine complexes on Swiss mice and zebrafish embryos.

Biomed Pharmacother 2018 Nov 25;107:1082-1092. Epub 2018 Aug 25.

Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, 74690-900, Brazil. Electronic address:

Anticancer potential of ruthenium complexes has been widely investigated, but safety evaluation studies are still scarce. Despite of ruthenium-based anticancer agents are known to cause fewer side effects compared to other metal-based drugs, these compounds are not fully free of toxicity, causing mainly nephrotoxicity. Based on the promising results from antitumor activity of the complexes [Ru(L-Met)(bipy)(dppb)]PF (RuMet) and [Ru(L-Trp)(bipy)(dppb)]PF (RuTrp), for the first time we investigated the toxicity profile of these complexes in rodent and zebrafish models. The acute oral toxicity was evaluated in Swiss mice. The mutagenic and genotoxic potential was determined by a combination of Micronucleus (MN) and Comet assay protocols, after exposure of Swiss mice to RuMet and RuTrp in therapeutic doses. Zebrafish embryos were exposed to these complexes, and their development observed up to 96 h post-fertilization. RuMet and RuTrp complexes showed low acute oral toxicity. Recorded behavioral changes were not recorded, nor were macroscopic morphological changes or structural modifications in the liver and kidneys. These complexes did not cause genetic toxicity, presenting a lack of micronuclei formation and low DNA damage induction in the cells from Swiss mice. In contradiction, cisplatin treatment exhibited high mutagenicity and genotoxicity. RuMet and RuTrp showed low toxicity in the embryo development of zebrafish. The RuMet and RuTrp complexes demonstrated low toxicity in the two study models, an interesting property in preclinical studies for novel anticancer agents.
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http://dx.doi.org/10.1016/j.biopha.2018.08.051DOI Listing
November 2018

Exposure to low concentration of fluoxetine affects development, behaviour and acetylcholinesterase activity of zebrafish embryos.

Comp Biochem Physiol C Toxicol Pharmacol 2019 Jan 6;215:1-8. Epub 2018 Sep 6.

Laboratório de Genética Toxicológica, Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília, Asa Norte, 70910-900 Brasília, Distrito Federal, Brazil.

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI) antidepressant widely used in clinics and very often found in environmental samples of urban aquatic ecosystems in concentrations ranging from ng/L to μg/L. Fish populations might be especially susceptible to FLX due to the presence of conserved cellular receptors of serotonin. Neurotoxic effects on fish biota of polluted water bodies may be expected, but there are no sufficient studies in the current literature to elucidate this hypothesis. Batteries of embryo larval assays with zebrafish were performed to evaluate the potential effects of FLX exposure, including environmentally relevant concentrations. Evaluated parameters included survival, development, behaviour and neuronal biochemical markers. Regarding acute toxicity, a 168 h-LC value of 1.18 mg/L was obtained. Moreover, hatching delay and loss of equilibrium were observed, but at a concentration level much higher than FLX measured environmental concentrations (>100 μg/L). On the other hand, effects on locomotor and acetylcholinesterase activity (≥0.88 and 6 μg/L, respectively) were found at levels close to the maximum reported FLX concentration in surface waters. Altogether, these results suggest that FLX is neurotoxic to early life stages of zebrafish, in a short period of time causing changes in important ecological attributes which can probably be linked from molecular to population level.
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http://dx.doi.org/10.1016/j.cbpc.2018.08.009DOI Listing
January 2019

Chronic effects of carbamazepine on zebrafish: Behavioral, reproductive and biochemical endpoints.

Ecotoxicol Environ Saf 2018 Nov 17;164:297-304. Epub 2018 Aug 17.

Departamento de Biologia e CESAM, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.

Carbamazepine (Cbz), one of the most prescribed pharmaceuticals in the world is often detected in surface waters and sediments. However, few studies addressed its chronic effects in fish. In the present study, Danio rerio adults were exposed for 63 days to Cbz (0 - control, 10 μg L - concentration found in effluents, and 10,000 μg L - 5% of LC at 72 h). Assessed endpoints were: feeding behavior, growth rate, number of eggs produced and their viability, histological alterations in female gonads, and biochemical biomarkers associated with antioxidant defenses (catalase - CAT, and glutathione S-transferase - GST activities), neurotransmission (acetylcholinesterase activity - AChE) and metabolism (lactate dehydrogenase - LDH). Cbz exposure increased the total time for food intake but did not affect D. rerio growth. Although the total number of eggs was not affected by Cbz exposure, the eggs viability was significantly impaired. Exposure to Cbz caused alterations in the female gonads follicular stages. In terms of biochemical endpoints, CAT activity in liver and gills, was sensitive to the pharmaceutical exposure presenting a decreased activity. AChE activity was induced in the head (both concentrations) and muscle (10,000 μg L). GST activity was increased in gills (both concentrations) but inhibited in the intestine. Concerning LDH, enzymatic activity was increased in the liver and decreased in muscle and gills. Several of the above-mentioned effects can be directly linked with effects at population level (e.g. feeding behavior) and occurred at environmental concentrations (the lowest concentration tested), thus serious concerns regarding risks posed by Cbz residues to fish populations arise with this study.
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http://dx.doi.org/10.1016/j.ecoenv.2018.08.015DOI Listing
November 2018

Exposure to ayahuasca induces developmental and behavioral alterations on early life stages of zebrafish.

Chem Biol Interact 2018 Sep 4;293:133-140. Epub 2018 Aug 4.

Laboratory of Embryology and Developmental Biology, Institute of Biology, University of Brasilia, Brasilia-DF, Brazil. Electronic address:

Ayahuasca is a psychoactive concoction prepared from the plants Banisteriopsis caapi and Psychotria viridis which are used ancestrally by Amazonian Indian populations and more recently, by Christian religious groups in Brazil and other countries. The aims of the present study were to identify the effects of ayahuasca on zebrafish embryo development and neurobehavior. Toxicity and developmental endpoints for zebrafish embryos were assessed from 0 to 1000 mg/L over 96 h of exposure. The effects on locomotor activity of zebrafish larvae were assessed using a video tracking system (ZebraBox) from 0 to 20 mg/L and after 120 and 144 h of exposure. The LC of ayahuasca in zebrafish was determined as 236.3 mg/L. Ayahuasca exposure caused significant developmental anomalies in zebrafish embryos, mainly at the highest concentration tested, including hatching delay, loss of equilibrium, edema and the accumulation of red blood cells. Embryo behavior was also significantly affected, with decreased locomotor activity at the highest concentration tested. These results are in accordance with data obtained in mammal studies highlighting the possible risks of uncontrolled use of ayahuasca. Further research employing more specific behavior analysis could provide additional data on both therapeutic benefits and possible toxicological risk of ayahuasca.
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http://dx.doi.org/10.1016/j.cbi.2018.08.001DOI Listing
September 2018

Electrochemical remediation of amoxicillin: detoxification and reduction of antimicrobial activity.

Chem Biol Interact 2018 Aug 18;291:162-170. Epub 2018 Jun 18.

Faculty of Pharmacy, Federal University of Goiás (UFG), Goiânia, Goiás, Brazil; National Institute for Alternative Technologies of Detection, Toxicological Evaluation and Removal of Micropollutants and Radioactives (CNPq: INCT-DATREM), UNESP, Institute of Chemistry, Araraquara, SP, Brazil. Electronic address:

Amoxicillin (AMX) is one of the most commonly prescribed antibiotics around the world to treat and prevent several diseases in both human and veterinary medicine. Incomplete removal of AMX during wastewater treatment contributes to its presence in water bodies and drinking water. AMX is an emerging contaminant since its impact on the environment and human health remains uncertain. This contribution was aimed to evaluate the electrochemical oxidation (EO) of AMX using different anodes in tap water, NaCl or NaSO solutions and to evaluate the potential toxicity of remaining AMX and its by-products on zebrafish early-life stages. Chemical intermediates generated after EO were determined by mass spectrometry and their resulting antimicrobial activity was evaluated. AMX did not induce significant mortality in zebrafish during extended exposure but affected zebrafish development (increased body length) from 6.25 mg/L to 25 mg/L and inhibited enzymatic biomarkers. Carbon modified with titanium oxide ([email protected]) anode achieved complete AMX removal in just a few minutes and efficiency of the supported electrolytes occurred in the following order: 0.1 M NaCl > 0.1 M NaSO > 0.01 M NaCl > tap water. The order of potential toxicity to zebrafish early life-stages related to lethal and sublethal effects was as follows: 0.1 M NaSO > 0.1 M NaCl >0.01 M NaCl = tap water. Additionally, the EO of AMX using [email protected] electrode with 0.01 M NaCl was able to inhibit the antimicrobial activity of AMX, reducing the possibility of developing bacterial resistance.
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http://dx.doi.org/10.1016/j.cbi.2018.06.017DOI Listing
August 2018

Humic acid attenuation of silver nanoparticle toxicity by ion complexation and the formation of a Ag coating.

J Hazard Mater 2018 07 11;353:173-181. Epub 2018 Apr 11.

Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Federal District, Brazil. Electronic address:

The use of silver nanoparticles (AgNPs) result in an inevitable contact with aquatic environments. Here we study the behavior of AgNPs and the developmental toxicity in zebrafish embryos exposed to these nanoparticles (0-10 mg/L) with and without the presence of HA (20 mg/L), using zebrafish facility water (ZFW) and zebrafish growing media (ZGM). The presence of cations and HA gave rise to a decrease in Ag ion release and ζ-potential, an increase in the hydrodynamic diameter and oxidation of the AgNP surface. The results show that the presence of HA and cations in the media, as well as the silver speciation, i.e., the unusual presence of Ag, decreases the toxicity of AgNPs (LC50: 1.19 mg/L; LC50: 3.56 mg/L), as well as silver bioavailability and toxicity in zebrafish embryos. Developmental alterations and the LC50 (1.19 mg/L) of AgNPs in ZFW were more relevant (p ≤ 0.05) than for AgNPs in ZGM (LC50 ˃ 10 mg/L). It was demonstrated that the bioaccumulation and toxicity of AgNPs depends on several factors including AgNPs concentration, nanoparticle aggregation, dissolved silver ions, speciation of silver ions, the amount of salt in the environment, the presence of humic substances and others, and different combinations of all of these factors.
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http://dx.doi.org/10.1016/j.jhazmat.2018.04.019DOI Listing
July 2018

Toxicological study of the degradation products of antineoplastic agent etoposide in commercial formulation treated by heterogeneous photocatalysis using SrSnO.

Environ Sci Pollut Res Int 2019 Feb 20;26(5):4224-4233. Epub 2018 Feb 20.

Instituto de Química, Universidade de Brasília-UnB, Campus Darcy Ribeiro, Asa Norte, Brasília, DF, CEP-70910-000, Brazil.

Etoposide is an antineoplastic agent used for treating lung cancer, testicular cancer, breast cancer, pediatric cancers, and lymphomas. It is a pollutant due to its mutagenic and carcinogenic potential. Disposal of waste from this drug is still insufficiently safe, and there is no appropriate waste treatment. Therefore, it is important to use advanced oxidative processes (AOPs) for the treatment and disposal of medicines like this. The use of strontium stannate (SrSnO) as a catalyst in heterogeneous photocatalysis reactions has emerged as an alternative for the removal of organic pollutants. In our study, SrSnO was synthesized by the combustion method and characterized by X-ray diffraction (XRD), Raman, UV-Vis, and scanning electron microscopy (SEM) techniques, obtaining a surface area of 3.28 m g with cubic and well-organized crystallinity and a band gap of 4.06 eV. The experimental conditions optimized for degradation of an etoposide solution (0.4 mg L) were pH 5 and catalyst concentration of 1 g L. The results showed that the degradation processes using SrSnO combined with HO (0.338 mol L) obtained total organic carbon removal from the etoposide solution, 97.98% (± 4.03 × 10), compared with TiO, which obtained a mineralization rate of 72.41% (± 6.95 × 10-3). After photodegradation, the degraded solution showed no toxicity to zebrafish embryos through embryotoxicity test (OECD, 236), and no genotoxicity using comet assay and micronucleus test.
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http://dx.doi.org/10.1007/s11356-018-1524-2DOI Listing
February 2019

In vitro genotoxicity and in vivo subchronic evaluation of the anti-inflammatory pyrazole compound LQFM021.

Chem Biol Interact 2017 Nov 7;277:185-194. Epub 2017 Sep 7.

Laboratório de Farmacologia e Toxicologia Celular - FarmaTec, Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, GO, Brazil. Electronic address:

Scientific evidences have highlighted 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM021) as a promising anti-inflammatory, analgesic and antinociceptive agent due to its effects on peripheral opioid receptors associated with activation of the nitric oxide/cGMP/K pathway. Despite these important pharmacological findings, toxicity data of LQFM021 are scarce. Thus, this study investigated the in vitro genotoxicity of LQFM021 through cytokinesis-block micronucleus assay (OECD Nº 487/2014). Moreover, zebrafish model was used to assess the embryotoxicity potential of LQFM021 using fish embryo toxicity test (OECD Nº 236/2013) with extended exposure to evaluate subchronic larval development. In vivo subchronic toxicity of LQFM021 in rats (OECD Nº 407/2008) was also conducted. This compound at the lower concentrations tested (3.1 and 31 μg/mL) did not promote changes in micronuclei frequency in HepG2 cells. However, in the higher concentrations of LQFM021 (310 and 620 μg/mL) triggered a significant increase of micronucleated HepG2 cells, showing an alert signal of potential genotoxicity. Regarding the oral treatment of rats with LQFM021 (62.5, 125 or 250 mg/kg) for 28 days, the main findings showed that LQFM021 promoted renal and liver changes in a dose-dependent manner, being irreversible damage for kidneys while liver tissue showed a recovery after 14 days post treatment. Regarding embryotoxicity, although the lower concentrations used did not show toxicity, the concentration of LQFM021 (39.8 and 100 mg/L) promoted malformations in zebrafish embryo-larvae stage, in especial cardiac tissue changes. In conclusion, anti-inflammatory compound LQFM021 seems to have some limiting factors as a new therapeutic option to be used orally and in high repeated doses, related to those found in the non-steroidal anti-inflammatory drugs (NSAIDs).
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http://dx.doi.org/10.1016/j.cbi.2017.09.004DOI Listing
November 2017

Genotoxic and mutagenic assessment of iron oxide (maghemite-γ-FeO) nanoparticle in the guppy Poecilia reticulata.

Chemosphere 2017 Sep 13;183:305-314. Epub 2017 May 13.

Laboratory of Cellular Behavior, Department of Morphology, Biological Sciences Institute, Federal University of Goiás, Goiânia, Goiás, Brazil.

The environmental risk of nanomaterials (NMs) designed and used in nanoremediation process is of emerging concern, but their ecotoxic effects to aquatic organism remains unclear. In this study, the citrate-coated (maghemite) nanoparticles (IONPs) were synthesized and its genotoxic and mutagenic effects were investigated in the female guppy Poecilia reticulata. Fish were exposed to IONPs at environmentally relevant iron concentration (0.3 mg L) during 21 days and the animals were collected at the beginning of the experiment and after 3, 7, 14 and 21 days of exposure. The genotoxicity and mutagenicity were evaluated in terms of DNA damage (comet assay), micronucleus (MN) test and erythrocyte nuclear abnormalities (ENA) frequency. Results showed differential genotoxic and mutagenic effects of IONPs in the P. reticulata according to exposure time. The IONP induced DNA damage in P. reticulata after acute (3 and 7 days) and long-term exposure (14 and 21 days), while the mutagenic effects were observed only after long-term exposure. The DNA damage and the total ENA frequency increase linearly over the exposure time, indicating a higher induction rate of clastogenic and aneugenic effects in P. reticulata erythrocytes after long-term exposure to IONPs. Results indicated that the P. reticulata erythrocytes are target of ecotoxicity of IONPs.
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http://dx.doi.org/10.1016/j.chemosphere.2017.05.061DOI Listing
September 2017

Association between interleukin 6 -174 G/C promoter gene polymorphism and runners' responses to the dietary ingestion of antioxidant supplementation based on pequi (Caryocar brasiliense Camb.) oil: a before-after study.

Genet Mol Biol 2016 Oct-Dec;39(4):554-566. Epub 2016 Oct 10.

Department of Genetics and Morphology, Institute of Biological Sciences, Universidade de Brasilia, Brasilia, DF, Brazil.

Exercise is a double-edged sword: when practiced in moderation, it increases the expression of antioxidant enzymes, but when practiced strenuously it causes oxidative stress and cell damage. In this context, polymorphisms in the interleukin (IL)-6 gene should be investigated better because they can influence performance, at least in exercise that generates oxidative stress and leads to muscular injuries with consequent inflammation. In this work, we investigated the influence of IL-6 -174 G/C polymorphism on tissue damage and inflammation markers, lipid peroxidation, hemogram and lipid profile of runners before and after ingestion of 400 mg of pequi oil in capsules supplied daily for 14 consecutive days. The IL-6 genotypes were associated with significant differences in lipid peroxidation, with the CC mutant having lower values. There were also significant differences among these genotypes in the response to supplementation with pequi oil, exercise-induced damage and C-reactive protein (CRP) levels. The best protection against damage was observed with the heterozygous genotype. Although the CC genotype showed an increase in CRP levels after supplementation, the lack of a positive correlation between triglycerides and high-sensitivity CRP in this mutant genotype after supplementation indicated a protective effect of pequi. These findings deserve further investigation, particularly with regard to the quantification of circulating IL-6 concentrations.
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http://dx.doi.org/10.1590/1678-4685-GMB-2015-0299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127149PMC
October 2016

Ecotoxicological assessment of glyphosate-based herbicides: Effects on different organisms.

Environ Toxicol Chem 2017 07 13;36(7):1755-1763. Epub 2016 Sep 13.

Faculty of Pharmacy, Federal University of Goiás, Goiânia, Goiás, Brazil.

Glyphosate-based herbicides are the most commonly used worldwide because they are effective and relatively nontoxic to nontarget species. Unlimited and uncontrolled use of such pesticides can have serious consequences for human health and ecological balance. The present study evaluated the acute toxicity and genotoxicity of 2 glyphosate-based formulations, Roundup Original (Roundup) and Glyphosate AKB 480 (AKB), on different organisms: cucumber (Cucumis sativus), lettuce (Lactuca sativa), and tomato (Lycopersicon esculentum) seeds, and microcrustacean Artemia salina and zebrafish (Danio rerio) early life stages. For the germination endpoint, only L. esculentum presented significant sensitivity to AKB and L. sativa to Roundup, whereas both formulations significantly inhibited the root growth of all species tested. Both AKB and Roundup induced significant toxicity to A. salina; both are classified as category 3, which indicates a hazard for the aquatic environment, according to criteria of the Globally Harmonized Classification System. However, Roundup was more toxic than AKB, with 48-h median lethal concentration (LC50) values of 14.19 mg/L and 37.53 mg/L, respectively. For the embryo-larval toxicity test, Roundup proved more toxic than AKB for the mortality endpoint (96-h LC50 values of 10.17 mg/L and 27.13 mg/L, respectively), whereas for the hatching parameter, AKB was more toxic than Roundup. No significant genotoxicity to zebrafish larvae was found. We concluded that AKB and Roundup glyphosate-based formulations are phytotoxic and induce toxic effects in nontarget organisms such as A. salina and zebrafish early life stages. Environ Toxicol Chem 2017;36:1755-1763. © 2016 SETAC.
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http://dx.doi.org/10.1002/etc.3580DOI Listing
July 2017

The lipidome, genotoxicity, hematotoxicity and antioxidant properties of andiroba oil from the Brazilian Amazon.

Genet Mol Biol 2016 May;39(2):248-56

Laboratório de Genética Toxicológica, Departamento de Genética e Morfologia, Instituto de Ciências Biológicas, Universidade de Brasília (UnB), Brasília, DF, Brazil.

Andirobeira is an Amazonian tree, the seeds of which produce a commercially valuable oil that is used in folk medicine and in the cosmetic industry. Andiroba oil contains components with anti-inflammatory, cicatrizing and insect-repellant actions. However, virtually nothing is known of the safety of this oil for humans. The aim of this work was therefore to investigate the hematotoxicity, genotoxicity and mutagenicity of andiroba oil using the comet and micronucleus assays, and to assess its antioxidant properties and lipidome as a means of addressing safety issues. For the experiments, andiroba oil was administered by gavage for 14 consecutive days in nulliparous female Swiss mice randomly distributed in four groups: negative control and three doses of oil (500, 1000 and 2000 mg/kg/day). These doses were chosen based on recommendations of the OECD guideline no. 474 (1997). GC/MS was used to investigate the free fatty acid, cholesterol and triterpene content of andiroba oil in a lipidomic analysis. No clinical or behavioral alterations were observed throughout the period of treatment, and exposure to andiroba oil at the doses and conditions used here did not result in hematotoxic, genotoxic or mutagenic effects. Tests in vitro showed that oil sample 3 from southwestern of Brazilian Amazon had a high antioxidant capacity that may protect biological systems from oxidative stress, although this activity remains to be demonstrated in vivo.
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http://dx.doi.org/10.1590/1678-4685-GMB-2015-0098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910557PMC
May 2016

Steroid androgen 17α-methyltestosterone induces malformations and biochemical alterations in zebrafish embryos.

Environ Toxicol Pharmacol 2016 Jun 27;44:107-13. Epub 2016 Apr 27.

Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília, Asa Norte, CEP 70910-900 Brasília, DF, Brazil. Electronic address:

The synthetic androgen 17α-methyltestosterone is widely used in fish aquaculture for sex reversion of female individuals. Little is known about the amount of MT residues reaching the aquatic environment and further impacts in non-target organisms, including fish early-life stages. Thus, in this work, zebrafish embryos were exposed to two forms of 17α-methyltestosterone: the pure compound (MT) and a formulation commonly used in Brazil (cMT). For MT, a 96h-LC50 of 10.09mg/l was calculated. MT also affected embryo development inducing tail malformations, edemas, abnormal development of the head, and hatching delay. At biochemical level MT inhibited vitellogenin (VTG) and inhibited cholinesterase and lactate dehydrogenase. cMT elicited similar patterns of toxicity as the pure compound (MT). Effects reported in this study suggest a potential environmental risk of MT, especially since the VTG effects occurred at environmental relevant concentrations (0.004mg/l).
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http://dx.doi.org/10.1016/j.etap.2016.04.014DOI Listing
June 2016

Genotoxic and histopathological biomarkers for assessing the effects of magnetic exfoliated vermiculite and exfoliated vermiculite in Danio rerio.

Sci Total Environ 2016 May 12;551-552:228-37. Epub 2016 Feb 12.

Department of Genetics and Morphology, Institute of Biological Sciences, Brasília University, Brasília, Brazil. Electronic address:

Magnetic exfoliated vermiculite is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. It was developed primarily to mitigate pollution, but the possible adverse impacts of its application have not yet been evaluated. In this context, the acute toxicity of magnetic exfoliated vermiculite and exfoliated vermiculite was herein assessed by genotoxic and histopathological biomarkers in zebrafish (Danio rerio). DNA fragmentation was statistically significant for all groups exposed to the magnetic exfoliated vermiculite and for fish exposed to the highest concentration (200mg/L) of exfoliated vermiculite, whereas the micronucleus frequency, nuclear abnormalities and histopathological alterations were not statistically significant for the fish exposed to these materials. In the intestinal lumen, epithelial cells and goblet cells, we found the presence of magnetic exfoliated vermiculite and exfoliated vermiculite, but no alterations or presence of the materials-test in the gills or liver were observed. Our findings suggest that the use of magnetic exfoliated vermiculite and exfoliated vermiculite during standard ecotoxicological assays caused DNA damage in D. rerio, whose alterations may be likely to be repaired, indicating that the magnetic nanoparticles have the ability to promote genotoxic damage, such as DNA fragmentation, but not mutagenic effects.
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http://dx.doi.org/10.1016/j.scitotenv.2016.01.048DOI Listing
May 2016

Toxicological Evaluation of a Potential Immunosensitizer for Use as a Mucosal Adjuvant--Bacillus thuringiensis Cry1Ac Spore-Crystals: A Possible Inverse Agonist that Deserves Further Investigation.

Toxins (Basel) 2015 Dec 9;7(12):5348-58. Epub 2015 Dec 9.

Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF 70.910-900, Brazil.

In addition to their applicability as biopesticides, Bacillus thuringiensis (Bt) Cry1Ac spore-crystals are being researched in the immunology field for their potential as adjuvants in mucosal and parenteral immunizations. We aimed to investigate the hematotoxicity and genotoxicity of Bt spore-crystals genetically modified to express Cry1Ac individually, administered orally (p.o.) or with a single intraperitoneal (i.p.) injection 24 h before euthanasia, to simulate the routes of mucosal and parenteral immunizations in Swiss mice. Blood samples were used to perform hemogram, and bone marrow was used for the micronucleus test. Cry1Ac presented cytotoxic effects on erythroid lineage in both routes, being more severe in the i.p. route, which also showed genotoxic effects. The greater severity noted in this route, mainly at 6.75 mg/kg, as well as the intermediate effects at 13.5 mg/kg, and the very low hematotoxicity at 27 mg/kg, suggested a possible inverse agonism. The higher immunogenicity for the p.o. route, particularly at 27 mg/kg, suggested that at this dose, Cry 1Ac could potentially be used as a mucosal adjuvant (but not in parenteral immunizations, due to the genotoxic effects observed). This potential should be investigated further, including making an evaluation of the proposed inverse agonism and carrying out cytokine profiling.
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http://dx.doi.org/10.3390/toxins7124881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690131PMC
December 2015

Short-term exposure to low doses of rotenone induces developmental, biochemical, behavioral, and histological changes in fish.

Environ Sci Pollut Res Int 2015 Sep 7;22(18):13926-38. Epub 2015 May 7.

Laboratório de Citogenética, Departamento de Genética, Instituto de Ciências Biológicas, Universidade Federal do Pará, Campus do Guamá, Av. Perimetral, Guamá, Belém, Pará, 66075-900, Brazil,

Rotenone, a natural compound derived from plants of the genera Derris and Lonchocarpus, is used worldwide as a pesticide and piscicide. This study aims to assess short-term toxicity of rotenone to early-life stages of the fish Danio rerio and Poecilia reticulata using a wide and integrative range of biomarkers (developmental, biochemical, behavioral, and histopathological). Moreover, the species sensitivity distribution (SSD) approach was used to compare rotenone acute toxicity to fish species. Toxicity tests were based on the OECD protocols, fish embryo toxicity test (for D. rerio embryos), and fish acute toxicity test (for P. reticulata juveniles). D. rerio embryos were used to estimate lethal concentrations and analyze embryonic and enzymatic alterations (activity of catalase, glutathione-S-transferase, and cholinesterase), while P. reticulata juveniles were used for the assessment of histological damage in the gills and liver. Rotenone induced significant mortality in zebrafish embryos with a 96-h lethal concentration 50% (LC50) = 12.2 μg/L. Rotenone was embryotoxic, affecting the development of D. rerio embryos, which showed cardiac edema; tail deformities; loss of equilibrium; and a general delay characterized by lack of tail detachment, delayed somite formation, yolk sac absorption, and lack of pigmentation. Biochemical biomarker inhibition was observed for concentrations ≥1 μg/L for CAT and glutathione-S-transferase (GST) and for cholinesterase (ChE) in concentration from 10 μg/L. Behavioral changes were observed for P. reticulata juveniles exposed to concentrations equal to or above 25 μg/L of rotenone; moreover, histological damage in the liver and gills of fish exposed to concentrations equal to or above 2.5 μg/L could be observed. A hazard concentration 5% (HC5) of 3.2 μg/L was estimated considering the acute toxicity data for different fish species (n = 49). Lethal and sublethal effects of rotenone raise a concern about its effects on nontarget fish species, especially because rotenone and its metabolite rotenolone are frequently reported in the microgram range in natural environments for several days after field applications. Rotenone should be used with caution. Given the high toxicity and wide range of sublethal effects here reported, further studies in a chronic exposure scenario are recommended.
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http://dx.doi.org/10.1007/s11356-015-4596-2DOI Listing
September 2015

Hematotoxicity and genotoxicity evaluations in Swiss mice intraperitoneally exposed to Bacillus thuringiensis (var kurstaki) spore crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2Aa.

Environ Toxicol 2016 Aug 21;31(8):970-8. Epub 2015 Apr 21.

Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasilia, Brasilia/DF, Brazil.

Bacillus thuringiensis (Bt) has been widely used in foliar sprays as part of integrated pest management strategies against insect pests of agricultural crops. Since the advent of genetically modified plants expressing Bt δ-endotoxins, the bioavailability of Cry proteins has increased, and therefore for biosafety reasons their adverse effects should be studied, mainly for nontarget organisms. We evaluated, in Swiss mice, the hematotoxicity and genotoxicity of the genetically modified strains of Bt spore crystals Cry1Aa, 1Ab, 1Ac, or 2Aa at 27 mg/kg, and Cry1Aa, 1Ab and 2Aa also at 136 and 270 mg/kg, administered with a single intraperitoneal injection 24 h before euthanasia. Controls received filtered water or cyclophosphamide. Blood samples collected by cardiac puncture were used to perform hemogram, and bone marrow was extracted for the micronucleus test. Bt spore crystals presented toxicity for lymphocytes when in higher doses, which varied according to the type of spore crystal studied, besides promoting cytotoxic and genotoxic effects for the erythroid lineage of bone marrow, mainly at highest doses. Although the profile of such adverse side effects can be related to their high level of exposure, which is not commonly found in the environment, results indicated that these Bt spore crystals were not harmless to mice. This suggests that a more specific approach should be taken to increase knowledge about their toxicological properties and to establish the toxicological risks to nontarget organisms. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 970-978, 2016.
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http://dx.doi.org/10.1002/tox.22106DOI Listing
August 2016